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Biomedical subjects

C A Jones

Publications and source records attributed to C A Jones.

At least 91 records · Page 5Linked to original sources

Serum creatinine levels in the US population: third National Health and Nutrition Examination Survey.

This report describes the distribution of serum creatinine levels by sex, age, and ethnic group in a representative sample of the US population. Serum creatinine level was evaluated in the third National Health and Nutrition Examination Survey (NHANES III) in 18,723 participants aged 12 years and older who were examined between 1988 and 1994. Differences in mean serum creatinine levels were compared for subgroups defined by sex, age, and ethnicity (non-Hispanic white, non-Hispanic black, and Mexican-American). The mean serum creatinine value was 0.96 mg/dL for women in the United States and 1.16 mg/dL for men. Overall mean creatinine levels were highest in non-Hispanic blacks (women, 1.01 mg/dL; men, 1.25 mg/dL), lower in non-Hispanic whites (women, 0.97 mg/dL; men, 1.16 mg/dL), and lowest in Mexican-Americans (women, 0.86 mg/dL; men, 1.07 mg/dL). Mean serum creatinine levels increased with age among both men and women in all three ethnic groups, with total US mean levels ranging from 0.88 to 1.10 mg/dL in women and 1.00 to 1.29 mg/dL in men. The highest mean creatinine level was seen in non-Hispanic black men aged 60+ years. In the total US population, creatinine levels of 1.5 mg/dL or greater were seen in 9.74% of men and 1.78% of women. Overall, among the US noninstitutionalized population, 10.9 million people are estimated to have creatinine values of 1.5 mg/dL or greater, 3.0 million have values of 1.7 mg/dL or greater, and 0.8 million have serum creatinine levels of 2.0 mg/dL or greater. Mean serum creatinine values are higher in men, non-Hispanic blacks, and older persons and are lower in Mexican-Americans. In the absence of information on glomerular filtration rate (GFR) or lean body mass, it is not clear to what extent the variability by sex, ethnicity, and age reflects normal physiological differences rather than the presence of kidney disease. Until this information is known, the use of a single cutpoint to define elevated serum creatinine values may be misleading.

Adolescent↗

Use of alternate splice sites in granule-bound starch synthase mRNA from low-amylose rice varieties.

The rice Waxy gene encodes a granule-bound starch synthase (GBSS) necessary for the synthesis of amylose in endosperm tissue. We have previously shown that a CT microsatellite near the transcriptional start site of the GBSS gene can distinguish 7 alleles that accounted for more than 80% of the variation in apparent amylose content in an extended pedigree of 89 US rice cultivars (Oryza sativa L.). Furthermore, all the cultivars with 18% or less amylose were shown to have the sequence AGTTATA at the putative leader intron 5' splice site, while all cultivars with a higher proportion of amylose had AGGTATA. Here we demonstrate that this single-base mutation reduces the efficiency of GBSS pre-mRNA processing and results in alternate splicing at three cryptic sites. The predominant 5' splice site in CT18 low-amylose varieties is 93 bp upstream of the splice site used in intermediate and high amylose varieties and is immediately 5' to the CT microsatellite that we previously demonstrated to be tightly correlated with amylose content. Use of the leader intron 5' splice site at either -93 or -1 in conjunction with the predominant 3' splice site results in formation of a small open reading frame 38 bp upstream of the normal ATG and out of frame with it. This open reading frame is not produced when any of the 5' leader intron splice sites are used in conjunction with an alternate 3' splice site five bases further downstream which was observed in all rice varieties tested.

Alternative Splicing↗

Differential regulation of IL-8 by IL-1beta and TNFalpha in hyaline membrane disease.

Mechanisms that regulate cytokine-mediated inflammation in the lungs of preterm infants, including factors which regulate production of the chemokine IL-8, remain poorly defined. Sequential bronchoalveolar lavage samples were obtained from preterm newborns with hyaline membrane disease over a 28-day period. Bronchoalveolar lavage cell cytokine relationships were evaluated and the differential regulation of IL-8 by IL-1beta and TNFalpha was studied in a short-term culture system. In vivo, IL-8 and IL-1beta protein levels correlated closely with each other and with macrophage counts. In cell culture, exogenous anti-IL-1beta antibody led to a 40% maximum inhibition (approximately) of IL-8 production by lipopolysaccharide stimulated lung inflammatory cells. Comparable amounts of exogenous anti-TNFalpha antibodies achieved a 15% maximum inhibition (approximately) of IL-8 production. Anti-IL-1beta and anti-TNFalpha antibodies in combination did not inhibit IL-8 production beyond that achieved by anti-IL-1beta antibody alone. These results, in preterm newborns, support the concept of lung inflammation mediated in part by a macrophage, IL-1beta, and IL-8 cell cytokine pathway. The results also suggest that factors other than IL-1beta and TNFalpha regulate IL-8 expression in the lungs of preterm infants.

Antibodies, Blocking↗

Maternal programming in asthma and allergy.

There has been increasing interest in the possibility that the mother has an important role to play in influencing the development of fetal and infant immune responses to allergens during gestation. This finding, by several groups, of specific immune responses of infants at birth to individual trigger factors associated with an underlying immaturity of cytokine production, is intriguing in the light of the development of subsequent allergic disease. The interactions between mother, placenta and fetus are now forming a focus for ongoing research and may be a potential target for intervention aimed at preventing allergic asthma.

Allergens↗

Simple nutritional indicators as independent predictors of mortality in hemodialysis patients.

A strong association exists between nutritional status and morbidity and mortality in patients with end-stage renal disease who are treated with hemodialysis. Described here is the predictive value for mortality over 5 years of follow-up of a number of risk factors, recorded at baseline, in a national sample of 3,607 hemodialysis patients. Among the variables studied were case-mix covariates, caregiver classifications of nutritional status, serum albumin concentration, and body mass index (BMI). The Case Mix Adequacy special study of the United States Renal Data System (USRDS) provided these measurements as of December 31, 1990. The USRDS patient standard analysis file provided follow-up data on mortality for all patients through December 31, 1995, by which time 64.7% of the patients had died. BMI is a simple anthropometric measurement that has received little attention in dialysis practice. Caregiver classification refers to documentation in a patient's dialysis facility medical records that stated an individual to be "undernourished/cachectic," "obese/overweight," or "well-nourished." The mean serum albumin was 3.7 +/- 0.45 (SD) g/dL, and the mean BMI was 24.4 +/- 5.3 (SD) kg/m2. By caregiver classification, 20.1% of patients were undernourished, and 24.9% obese. In hazard regression models, including but not limited to the Cox proportional hazards model, low BMI, low serum albumin, and the caregiver classification "undernourished" were independently and significantly predictive of increased mortality. In analyses allowing for time-varying relative mortality risks (ie, nonproportional hazards), the greatest predictive value of all three variables occurred early during follow-up, but the independent predictive value of baseline serum albumin and BMI measurements on mortality risk persisted even 5 years later. No evidence of increasing mortality risk was found for higher values of BMI. Serum albumin was confirmed to be a useful predictor of mortality risk in hemodialysis patients; BMI was established as an independently important predictor of mortality; both serum albumin and BMI, measured at baseline, continue to possess predictive value 5 years later; the subjective caregiver classification of nutritional status "undernourished" has independent value in predicting mortality risk beyond the information gained from two other markers of nutritional status--BMI and serum albumin.

Adult↗

Noncompliance in hemodialysis: predictors and survival analysis.

Noncompliance with hemodialysis (HD), depending on the definition, occurs in 2% to more than 50% of patients. To better understand predictors and outcomes of noncompliance, we evaluated patient characteristics associated with noncompliance and the impact of noncompliance on survival. Using data from two USRDS special studies, we identified 6,251 patients who were on dialysis for more than 1 year for inclusion in this study. Noncompliance was defined in four ways: skipping one or more HD sessions in a month, shortening by 10 or more minutes one or more HD sessions in a month, an interdialytic weight gain (IWG) of more than 5.7% of dry weight, or a serum phosphate (PO4) of greater than 7.5 mg/dL. Sociodemographic predictors of noncompliance were identified using logistic regression. Survival analysis was done using Cox proportional hazards models with adjustments for sociodemographics, comorbid conditions, and dose of HD. Overall, 8.5% of patients skipped HD, 20% shortened HD (7% three or more times), 10% had more than a 5.7% IWG, and 22% had a PO4 greater than 7.5. There was a significant correlation among the measures of noncompliance. Blacks (adjusted odds ratio [AOR] = 2.10), patients aged 20 to 39 years (AOR = 1.62), and smokers (AOR = 1.34) were significantly more likely to skip HD than whites, patients aged 40 to 59 years, and nonsmokers, respectively (P < 0.01 for each). Similar results were seen for the other measures of noncompliance, except for PO4, in which blacks were significantly less likely to be noncompliant (NC) (AOR = 0.85, P < 0.05). Compared with compliant patients, those who skipped one or more HD sessions in a month had a 25% higher risk of death (P < 0.01). Those who had greater than a 5.7% IWG had a 35% higher risk of death (P < 0.001), whereas those with a PO4 > 7.5 had a 13% higher risk of death (P < 0.05). Overall, patients who shortened HD sessions did not have a higher risk of death, but those who shortened three or more in 1 month had a 20% higher risk of death (P < 0.05). Compliance with a medical regimen is a complex issue. Noncompliance in HD often, but not always, is associated with a higher risk of an adverse outcome. This is a US government work. There are no restrictions on its use.

Adult↗

The Drosophila esc and E(z) proteins are direct partners in polycomb group-mediated repression.

The extra sex combs (esc) and Enhancer of zeste [E(z)] proteins are members of the Drosophila Polycomb group (Pc-G) of transcriptional repressors. Here we present evidence for direct physical interaction between the esc and E(z) proteins using yeast two-hybrid and in vitro binding assays. In addition, coimmunoprecipitation from embryo extracts demonstrates association of esc and E(z) in vivo. We have delimited the esc-binding domain of E(z) to an N-terminal 33-amino-acid region. Furthermore, we demonstrate that site-directed mutations in the esc protein previously shown to impair esc function in vivo disrupt esc-E(z) interactions in vitro. We also show an in vitro interaction between the heed and EZH1 proteins, which are human homologs of esc and E(z), respectively. These results suggest that the esc-E(z) molecular partnership has been conserved in evolution. Previous studies suggested that esc is primarily involved in the early stages of Pc-G-mediated silencing during embryogenesis. However, E(z) is continuously required in order to maintain chromosome binding by other Pc-G proteins. In light of these earlier observations and the molecular data presented here, we discuss how esc-E(z) protein complexes may contribute to transcriptional silencing by the Pc-G.

Amino Acid Sequence↗

Development and progression of microalbuminuria in a clinic sample of patients with insulin dependent diabetes mellitus.

The evolution of abnormal albumin excretion and its association with suggested risk factors were studied in 233 children with insulin dependent diabetes mellitus (IDDM) attending a single paediatric diabetic clinic over an eight year period. Yearly albumin:creatinine ratios (ACR; measured in mg/mmol) in early morning urine samples, glycated haemoglobin (HbA1c), and blood pressure were recorded. Thirty four (14.5%) children had a persistently raised ACR (ACR > or = 2.5 mg/mmol on at least three consecutive occasions) and 21 (9%) had an intermittently raised ACR (ACR > or = 2.5 mg/mmol on at least two occasions). Factors associated with a persistently raised ACR compared with normal albuminuria in IDDM included longer duration of diabetes, raised median HbA1c during the first five years after diagnosis, and final age adjusted systolic and diastolic blood pressure represented as standard deviation scores. The onset of persistently raised ACR in 13 of 34 children was before puberty and in 23 of 34 children it was within the first four years of diagnosis. The cross sectional prevalence of raised ACR was 12.9% at one year, 18.3% at five years, and 33% at 10 years after diagnosis. Raised ACR occurs frequently before puberty and in the early stages of childhood diabetes.

Age of Onset↗

Isolation and characterisation of an antifungal antibiotic (GR135402) with protein synthesis inhibition.

A novel antifungal antibiotic GR135402 has been isolated from a fermentation broth of Graphium putredinis which inhibited protein synthesis in Candida albicans but not rabbit reticulocytes. The spectrum of activity included C. albicans and Cryptococcus neoformans but not some other Candida species or Aspergillus species. Therapeutic efficacy in a mouse model of systemic candidosis was attained following parenteral dosing.

Animals↗

Paradoxical effect of oxygen administration on breathing stability following post-hyperventilation apnoea in lambs.

1. Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body activity, and yet earlier experiments in neonates have shown that PB incidence may be increased following the application of hyperoxia. To clarify this paradox, we studied the changes in the pattern of PB that occur following administration of oxygen in a lamb model of PB. 2. PB was induced in eleven of seventeen anaesthetized lambs following passive hyperventilation with air. When oxygen was administered during PB, the pattern was first enhanced, as evidenced by a sudden decrease in the ratio of the ventilatory duration to the apnoeic pause duration, and then suppressed, as evidenced by a progressive return to stable breathing which was associated with an increase in minute ventilation. 3. Five of the six lambs that did not show PB following passive hyperventilation with air could be made to do so if oxygen was substituted for air as the inspired gas following passive hyperventilation. 4. Five of the eleven lambs that showed PB following hyperventilation with air responded to the application of oxygen during PB by switching to a gross form of episodic breathing consisting of long apnoeic pauses followed by equally long periods of breathing during which minute ventilation fell progressively with time. 5. We conclude that when applied against a background of arterial hypoxaemia, oxygen has a destabilizing influence on ventilation in that (a) it accentuates the unstable breathing that occurs during PB, (b) it induces PB in lambs that exhibited stable breathing in air, and (c) it may precipitate episodic breathing.

Animals↗

An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice.

The product of the scl (also called tal-1 or TCL5) gene is a basic domain, helix-loop-helix (bHLH) transcription factor required for the development of hematopoietic cells. Additionally, scl gene disruption and dysregulation, by either chromosomal translocations or a site-specific interstitial deletion whereby 5' regulatory elements of the sil gene become juxtaposed to the body of the scl gene, is associated with T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma. Here we show that an inappropriately expressed scl protein, driven by sil regulatory elements, can cause aggressive T-cell malignancies in collaboration with a misexpressed LMO1 protein, thus recapitulating the situation seen in a subset of human T-cell ALL. Moreover, we show that inappropriately expressed scl can interfere with the development of other tissues derived from mesoderm. Lastly, we show that an scl construct lacking the scl transactivation domain collaborates with misexpressed LMO1, demonstrating that the scl transactivation domain is dispensable for oncogenesis, and supporting the hypothesis that the scl gene product exerts its oncogenic action through a dominant-negative mechanism.

Animals↗

Biosynthesis of renin in mouse kidney tumor As4.1 cells.

As4.1, a renin-expressing cell line isolated from a mouse renal tumor, was characterized for synthesis, processing, storage and secretion of renin polypeptides. Metabolic labeling, immunoprecipitation and SDS/PAGE analysis revealed that renin was secreted into the culture supernatant predominantly in the form of prorenin which migrated as products of 42-47 kDa. The predominant intracellular renin was processed into two chains, of 33-34 and 5 kDa. N-glycanase treatment removed N-linked oligosaccharides and yielded products of 41 kDa for prorenin and 31-32 kDa for the heavier chain of two-chain renin. The N-terminus of the constitutively secreted prorenin was determined by automated Edman degradation to be Leu22 while the N-terminus of the heavy chain was Ser72. Renin polypeptides constituted 3.1 +/- 1.4% (mean percentage of total precipitable radioactivity +/- SD) of de-novo-synthesized protein secreted into the medium and 0.2 +/- 0.17% retained intracellularly. Extrapolation of renin activity assays suggest that a single cell stores approximately 680 fg of active renin. A slow incremental release into the medium of processed renin heavy chain was detected by immunoprecipitation and SDS/PAGE. Renin activity assays confirmed the release of approximately 4 fg prorenin and 0.32 fg active renin cell(-1) h(-1). Indirect immunofluorescence demonstrated intracellular renin to be distributed in a punctate pattern. Renin was found to be colocalized with the lysosomal marker, beta-glucuronidase, by double-fluorescent labeling. These cells have enabled characterization of glycosylated mouse renin-1 and may prove a valuable tool for studying intracellular trafficing of renin and associated processing enzymes.

Animals↗

Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo.

OBJECTIVE: To investigate the effects of adenosine receptor agonists and antagonists on 5-HT release from rat isolated pleural mast cells and on plasma protein extravasation in the skin of conscious rats. In vitro METHODS: Rat isolated pleural mast cells were loaded with [14C] 5-HT, sensitised with mouse monoclonal anti-DNP and then challenged with human serum albumin-DNP. DNP-stimulated 5-HT release from mast cells was determined. In vivo METHODS: Rats, loaded intravenously with [125I] human serum albumin, were injected intradermally with adenosine agonists at sites on the back. 30 min later plasma protein extravasation at each injection site was determined. RESULTS: In isolated mast cells, each adenosine agonist enhanced DNP-induced 5-HT release, N6-(3-iodobenzyl)-5-(N-methyl-carboxamidoadenosine), (IB-MECA), being the most potent agonist. The adenosine A1/A2 antagonist, 8-phenyltheophylline (8-PT), had no effect on the response to IB-MECA. In contrast, 3-(4-amino-iodobenzyl)-8-[4-[[[carboxy]methyl]oxy]phenyl]-1-propylxanthi ne, (I-ABOPX), inhibited (pA2 6.2) the IB-MECA responses. In the skin of conscious rats, intradermal IB-MECA produced a marked plasma protein extravasation (PPE) which was mimicked by N6-2-(4-aminophenyl)-ethyladenosine (APNEA). The PPE produced by IB-MECA was not affected by either 8-PT or CGS15943A, but was virtually abolished by cyproheptadine and in rats pre-treated with Compound 48/80. CONCLUSIONS: These results indicate that stimulation of adenosine A3 receptors both enhances degranulation in vitro and directly produces degranulation of rat mast cells in vivo.

Adenosine↗

Epidemiology of interstitial cystitis.

OBJECTIVES: To discuss what is currently known about the population prevalence of interstitial cystitis (IC) and demographic characteristics of IC patients. METHODS: Changes over time in the criteria for diagnosis of IC are described. The 3 published studies of the population prevalence of IC are reviewed. Epidemiologic issues important in the design of studies of IC are cited. RESULTS: IC is a disease of chronic voiding symptoms. There is very little reliable information published on the etiology, risk factors, or number of persons affected. The criteria used for diagnosis of IC by different investigators have been variable. In 1988, research criteria for a case definition of IC were published, to be applied for IC patients enrolled in National Institutes of Health-funded studies. Three published studies of the population prevalence of IC are available. Each study used different criteria for defining a case of IC, and none used the NIH research criteria to define a case. Prevalence estimates for IC vary significantly, from 10 cases/100,000 reported in Finland in 1975, (based on hospital record review), to 30/100,000 in the United States in 1987, (based on a mailed survey of board certified urologists), to 510 cases/100,000 in the United States in 1989, (based on participant self-report in the 1989 National Health Interview Survey). It is unclear the extent to which these estimates represent true differences in prevalence, rather than reflect the different methods used to define an IC case. Several investigators have reported demographic characteristics of the IC patients followed in their clinics. All studies of adults show a marked female predominance, with reported onset of symptoms generally in the middle years of life. Patients may experience a delay of years from the onset of symptoms to the time of definitive diagnosis. The natural history of symptoms of IC has been reported to be that of a subacute onset with a rapid peak in severity, and then a relatively constant plateau of chronic symptoms thereafter. However, many patients do experience remissions and flares in their disease symptoms. CONCLUSIONS: Few therapies for IC have been evaluated using rigorous epidemiologic methods. Many questions remain to be answered. New studies of IC should include epidemiologic consultation at the stage of study design.

Cystitis, Interstitial↗

Growth rates in pediatric dialysis patients and renal transplant recipients.

We compared growth rates by modality over a 6- to 14-month period in 1,302 US pediatric end-stage renal disese (ESRD) patients treated during 1990. Modality comparisons were adjusted for age, sex, race, ethnicity, and ESRD duration using linear regression models by age group (0.5 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 18 years). Growth rates were higher in young children receiving a transplant compared with those receiving dialysis (ages 0.5 to 4 years, delta = 3.1 cm/yr v continuous cycling peritoneal dialysis [CCPD], P < 0.01; ages 5 to 9 years, delta = 2.0 to 2.6 cm/yr v CCPD, chronic ambulatory peritoneal dialysis (CAPD), and hemodialysis, P < 0.01). In contrast, growth rates in older children were not statistically different when comparing transplantation with each dialysis modality. For most age groups of transplant recipients, we observed faster growth with alternate-day versus daily steroids that was not fully explained by differences in allograft function. Younger patients (<15 years) grew at comparable rates with each dialysis modality, while older CAPD patients grew faster compared with hemodialysis or CCPD patients (P < 0.02). There was no substantial pubertal growth spurt in transplant or dialysis patients. This national US study of pediatric growth rates with dialysis and transplantation shows differences in growth by modality that vary by age group.

Adolescent↗

Isolation of chromosome-specific paints from high-resolution flow karyotypes of the sheep (Ovis aries).

High-resolution bivariate flow karyotypes were obtained using fibroblast cell lines from a sheep with a normal karyotype (2n = 54), from sheep carrying Robertsonian translocation chromosomes and from sheep-hamster somatic cell hybrids. By taking advantage of the presence of chromosome polymorphisms, translocation chromosomes and sheep-hamster somatic cell hybrids, all sheep chromosomes were isolated by flow sorting. Chromosome-specific paints were generated from each sorted peak using degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). The sheep chromosome present in each peak was identified by chromosome-specific microsatellite analysis of the DOP-PCR products and fluorescence in situ hybridization (FISH) onto DAPI-banded sheep metaphase chromosomes. The chromosome-specific DNA obtained in this study can be used for the production of genomic libraries and as a resource for mapping randomly cloned DNA sequences that will greatly aid the construction of genetic and physical maps in the sheep. The chromosome-specific paints will facilitate chromosome identification and contribute to the study of karyotype evolution in the sheep and related species.

Animals↗